Time-resolved second harmonic generation (SHG) spectroscopy is used to investigate acetaminophen (APAP)-induced changes in the adsorption and transport properties of malachite green isothiocyanate ...(MGITC) dye to the surface of unilamellar 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes in an aqueous colloidal suspension. The adsorption of MGITC to DOPC liposome nanoparticles in water is driven by electrostatic and dipole–dipole interactions between the positively charged MGITC molecules and the zwitterionic phospholipid membranes. The SHG intensity increases as the added MGITC dye concentration is increased, reaching a maximum as the MGITC adsorbate at the DOPC bilayer interface approaches a saturation value. The experimental adsorption isotherms are fit using the modified Langmuir model to obtain the adsorption free energies, adsorption equilibrium constants, and the adsorbate site densities to the DOPC liposomes both with and without APAP. The addition of APAP is shown to increase MGITC adsorption to the liposome interface, resulting in a larger adsorption equilibrium constant and a higher adsorption site density. The MGITC transport times are also measured, showing that APAP decreases the transport rate across the DOPC liposome bilayer, especially at higher MGITC concentrations. Studying molecular interactions at the colloidal liposome interface using SHG spectroscopy provides a detailed foundation for developing potential liposome-based drug-delivery systems.
This work presents two searches for new physics characterized by pair-production of strongly interacting particles, each decaying to hadronic jets and a particle that is not detectable. The searches ...use the full 13 TeV proton-proton collision dataset produced by CERN’s Large Hadron Collider and recorded by the CMS detector from 2016 to 2018, with total integrated luminosity 137 fb−1. The presence of particles interacting too weakly to be detected is inferred using imbalance in the transverse momentum of the collision products, and sensitivity to pair- production is enhanced by requiring large values of the kinematic variable MT2 in events with at least two jets. The first search is inclusive, binning events using the total hadronic transverse energy, the total number of jets, the number of jets reconstructed as originating from a bottom quark, and either the value of MT2 in multijet events, or the transverse momentum of the jet in monojet events. The second search extends the first, by requiring the presence of a disappearing track in the event, and adds binning in the length and transverse momentum of the disappearing track. Both searches are sensitive to a variety of extensions to the Standard Model that include dark matter candidates. Of greatest interest, the results set constraints on pair production of squarks and gluinos as predicted by R-parity conserving supersymmetric extensions of the Standard Model, in which the lightest supersymmetric particle is a neutralino. The first search is sensitive to any decay chain terminating in Standard Model hadrons plus the neutralino, while the second specifically targets, with greatly enhanced sensitivity, decay chains containing an intermediate long-lived chargino. These constraints are the most stringent yet produced by any experiment.
A well-rounded introduction to work in a STEM laboratory is vital to scientific education. Besides the ability to use available instrumentation for sample characterization, students should also be ...imparted knowledge in the steps of instrument development and construction. These concepts can be taught using the example of lipid vesicle preparation via extrusion. Vesicle extrusion is a common technique that involves syringes pushing solutions through membrane filters and is used in fundamental studies on vesicles. Such research is important to better understand of biological phenomena and drug development. Well prepared samples are key to successful research. While the manual approach is very useful to acquire experience, automatic extrusion is more convenient, and automation often results in better reproducibility. These advantages can be combined in a simplistic automatic extruder, that does not require advanced technical skills to be assembled. It can therefore be used by various groups, ranging undergraduate to graduate students using equipment typically available. Using this approach, students can acquire different skillsets including coding, testing, and advanced use of building materials based on their properties. Finally, the quality of the automatic extruder is verified.
Magnesium oxide (MgO) is representative of the rocky materials comprising the mantles of terrestrial planets, such that its properties at high temperatures and pressures reflect the nature of ...planetary interiors. Shock-compression experiments on MgO to pressures of 1.4 terapascals (TPa) reveal a sequence of two phase transformations: from B1 (sodium chloride) to B2 (cesium chloride) crystal structures above 0.36 TPa, and from electrically insulating solid to metallic liquid above 0.60 TPa. The transitions exhibit large latent heats that are likely to affect the structure and evolution of super-Earths. Together with data on other oxide liquids, we conclude that magmas deep inside terrestrial planets can be electrically conductive, enabling magnetic field—producing dynamo action within oxide-rich regions and blurring the distinction between planetary mantles and cores.
Background
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the ...virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterized by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described.
Methods
We used an exhaustive database of human CCHF occurrence records and a niche modeling framework to map the global distribution of risk for human CCHF occurrence.
Results
A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region.
Conclusions
These new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans.
When humans are engaged in goal-related processing, activity in prefrontal cortex is increased 1, 2. However, it has remained unclear whether this prefrontal activity encodes a subject's current ...intention 3. Instead, increased levels of activity could reflect preparation of motor responses 4, 5, holding in mind a set of potential choices 6, tracking the memory of previous responses 7, or general processes related to establishing a new task set. Here we study subjects who freely decided which of two tasks to perform and covertly held onto an intention during a variable delay. Only after this delay did they perform the chosen task and indicate which task they had prepared. We demonstrate that during the delay, it is possible to decode from activity in medial and lateral regions of prefrontal cortex which of two tasks the subjects were covertly intending to perform. This suggests that covert goals can be represented by distributed patterns of activity in the prefrontal cortex, thereby providing a potential neural substrate for prospective memory 8–10. During task execution, most information could be decoded from a more posterior region of prefrontal cortex, suggesting that different brain regions encode goals during task preparation and task execution. Decoding of intentions was most robust from the medial prefrontal cortex, which is consistent with a specific role of this region when subjects reflect on their own mental states.
Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains ...controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging.
We included consecutive patients who were considered for cardiac transplant from 2006 to 2015. Serum alloantibodies were detected with single-antigen beads on the Luminex platform (One Lambda Inc., Canoga Park, CA). Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. cPRA was determined at multiple times. LVAD-associated allosensitization was defined as development of cPRA > 10% in patients with cPRA ≤ 10% before LVAD implantation. Post-transplant outcomes of interest were acute cellular rejection (ACR), antibody-mediated rejection (AMR), and survival.
Allosensitization status was evaluated in 268 patients (20% female). Mean age was 52 ± 12 years, and 132 (49.3%) received CF LVADs. After LVAD implant, 30 patients (23%) became newly sensitized, and the level of sensitization appeared to diminish in many of these patients while awaiting transplant. During the study period, 225 of 268 patients underwent transplant, and 43 did not. A CF LVAD was used to bridge 50% of the transplant recipients. Compared with patients without new sensitization or those already sensitized at baseline, the patients with LVAD-associated sensitization had a higher risk of ACR (p = 0.049) and higher risk of AMR (p = 0.018) but a similar intermediate-term post-transplant survival. The patients who did not receive a transplant had higher level of allosensitization, with a baseline cPRA of 20% vs 6% in those who received an allograft and a high risk (40%) of death during follow-up.
New allosensitization takes place in > 20% of patents supported with CF LVADs. Among patients who undergo transplant, this results in a higher risk of ACR and AMR, but survival remains favorable, likely due to the efficacy of current management after transplant. However, mortality in sensitized patients who do not reach transplant remains high, and new approaches are necessary to meet the needs of this group of patients.
The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could ...prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10-1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998-2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses.
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